State of the art of services in Europe: where are the problems?

International audiencen.

WHO International Classification of Diseases (ICD) Revision Process: incorporating rare diseases into the classification scheme: state of art

International audiencen.

New functionalities in Orphanet for orphan drugs, R&D and marketing authorisations to better serve the rare diseases community

International audiencen.

Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders

Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and natural history data and publications on these aspects have contributed to the knowledge and awareness of these rare diseases. However, for the assessment of long-term outcomes and for cost-effectiveness, the incompleteness and variable quality of the data raises concerns on the usefulness of these registries. The existing registries for orphan drug treatments for lysosomal storage disorders (LSD's) illustrate these limitations. LSD's are inherited disorders of lysosomal metabolism with a wide variety in clinical symptoms, ranging from severe life-threatening neurological disease to mild or even asymptomatic cases. Their prevalence is extremely low and thus data is scarce and scattered all over Europe. In the past few years, several enzyme replacement therapies and an oral substrate inhibitor have been developed which provide lifelong treatment of LSD's. For Fabry disease, two enzymes were authorized at the same time resulting in two different drug registries being required by the European Medicines Agency (EMA) to monitor effectiveness and safety. This has lead to patient data being divided between two separate registries which may have contributed to delays in the assessment of important outcomes. Three treatments (including a recently approved new enzyme) have now been authorized for Gaucher Disease and two other potential therapies are in the pipeline. Dividing up the data on Gaucher disease patients in to five separate registries benefits nobody. We argue that disease specific (rather than drug specific) registries, supervised by independent clinicians are urgently needed for the best long-term evaluation of treatments of these rare diseases